Preventing changes in mental health in a rat model of spinal cord injury

Spinal cord injury (SCI) leads to complex secondary consequences affecting among others the immune system, the digestive system, and mental health. Depression and anxiety have become major challenges in individuals with SCI as well as diseases of the brain. Post-SCI depression and anxiety likely affect not only the quality of life, but possibly also the ability of individuals to vigorously engage in rehabilitative training, which is currently one of the most effective treatments to restore moderate function. Besides chronic pain, injury induced inflammation is a frequently proposed connection to depression and/or anxiety disorders after various injuries of the nervous system. Evidence for this relation has been discussed, for example, after traumatic brain injury or stroke, multiple sclerosis, and spinal cord injury. A possible link is thus the exposure to pathogens that elicit inflammation. Rats with SCI are likely exposed to pathogens indirectly via changes in the gut microbiome (dysbiosis). Dysbiosis is known to increase the gut permeability and bacterial translocation. We detected in rats with cervical lesions significant anxiety (as tested in the elevated plus maze) and anhedonia (tested using the sucrose preference test) in parallel to gut microbiome changes. We will expand these results and link changes in the gut microbiome to mental health changes following SCI. Furthermore, we will show that preventing or decreasing these mental health changes will improve the efficacy of rehabilitative training in a forelimb reaching task. We will dampen microbiome changes by either the administration of fecal slurries from healthy rats or probiotics. We have exciting preliminary results indicating that rats treated with fecal slurries over the first days following SCI showed strongly improved performance in the elevated plus maze when compared to controls. In combination with developing a robust animal model for studying mental health changes after SCI, the proposed experiments will guide future treatment approaches for dampening such changes and to improve the efficacy of rehabilitative training. (CHN: SCIRTS chn:wdg)